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1.
Ren Fail ; 46(2): 2398709, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39252176

ABSTRACT

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.


Subject(s)
Acetates , Citric Acid , Dialysis Solutions , Hemodiafiltration , Humans , Retrospective Studies , Hemodiafiltration/methods , Female , Male , Middle Aged , Aged , Acetates/administration & dosage , Dialysis Solutions/administration & dosage , Dialysis Solutions/chemistry , Citric Acid/administration & dosage , Anticoagulants/administration & dosage , Kidney Failure, Chronic/therapy , Heparin/administration & dosage
2.
J Cell Mol Med ; 28(17): e70075, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39245800

ABSTRACT

Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.


Subject(s)
Erectile Dysfunction , Hyperuricemia , Inflammasomes , Janus Kinase 2 , NLR Family, Pyrin Domain-Containing 3 Protein , Rats, Sprague-Dawley , STAT3 Transcription Factor , Signal Transduction , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Janus Kinase 2/metabolism , Male , Inflammasomes/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Rats , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Erectile Dysfunction/metabolism , Hyperuricemia/drug therapy , Hyperuricemia/complications , Apoptosis/drug effects , Disease Models, Animal
3.
Iran J Basic Med Sci ; 27(10): 1293-1299, 2024.
Article in English | MEDLINE | ID: mdl-39229581

ABSTRACT

Objectives: This study was conducted to explore the impact of 1, 8-cineole (eucalyptol) on the biochemical, molecular, and histological changes caused by lead acetate in the liver of adult male Wistar rats. The research also investigated the potential involvement of the TLR4 signaling pathway in this effect. Materials and Methods: Rats were orally administered lead acetate (25 mg/kg-day) for 14 consecutive days and received 1, 8-cineole (100 mg/kg-day) during the same period. Results: 1, 8-cineole prevented an increase in the malondialdehyde level, a decrease in the glutathione level, and a decrease in the activity of superoxide dismutase and glutathione peroxidase enzymes in the liver of rats treated with lead acetate. This monoterpene also prevented an increase in the expression of pro-inflammatory cytokines and significantly reduced the infiltration of inflammatory cells in the liver parenchyma. Additionally, 1, 8-cineole discouraged the increase in toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) expression in the liver and stopped a rise in serum AST and ALT enzymes. Conclusion: 1, 8-cineole can prevent liver damage caused by lead acetate by reducing oxidative stress and inflammation. This hepatoprotection is probably achieved by inhibiting TLR4/MyD88/NF-κB signaling.

4.
Article in English | MEDLINE | ID: mdl-39236428

ABSTRACT

This work for the first time reported the complete transformation of 17ß-estradiol (E2) to estrone (E1) by unknown wild-type enzyme present in the widely used commercial arylsulfatase derived from Helix pomatia. It was found that acetate could effectively inhibit the unknown enzyme with a half inhibitory concentration (IC50) of 140.9 µM, while phosphate and citrate showed no inhibition. Since the buffer solutions with phosphate and citrate have been used in the enzymatic hydrolysis of natural estrogen conjugates for decades, the transformation of E2 to E1 likely occurred during such procedure, inevitably leading to overestimated E1, but underestimated E2. It was further suggested that acetate should be used to prevent this undesirable transformation during the enzymatic hydrolysis of natural estrogen conjugates.

5.
AAPS PharmSciTech ; 25(7): 202, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237685

ABSTRACT

The focus of the present work was to develop amorphous solid dispersion (ASD) formulation of aprepitant (APT) using sucrose acetate isobutyrate (SAIB) excipient, evaluate for physicochemical attributes, stability, and bioavailability, and compared with hydroxypropyl methylcellulose (HPMC) based formulation. Various formulations of APT were prepared by solvent evaporation method and characterized for physiochemical and in-vivo performance attributes such as dissolution, drug phase, stability, and bioavailability. X-ray powder diffraction indicated crystalline drug conversion into amorphous phase. Dissolution varied as a function of drug:SAIB:excipient proportion. The dissolution was more than 80% in the optimized formulation (F10) and comparable to HPMC based formulation (F13). Stability of F10 and F13 formulations stored at 25 C/60% and 40°C/75% RH for three months were comparable. Both ASD formulations (F10 and F13) were bioequivalent as indicated by the pharmacokinetic parameters Cmax and AUC0-∞. Cmax and AUC0-∞ of F10 and F13 formulations were 2.52 ± 0.39, and 2.74 ± 0.32 µg/ml, and 26.59 ± 0.39, and 24.79 ± 6.02 µg/ml.h, respectively. Furthermore, the bioavailability of ASD formulation was more than twofold of the formulation containing crystalline phase of the drug. In conclusion, stability and oral bioavailability of SAIB based ASD formulation is comparable to HPMC-based formulation of poorly soluble drugs.


Subject(s)
Biological Availability , Excipients , Solubility , Sucrose , Sucrose/analogs & derivatives , Sucrose/chemistry , Administration, Oral , Animals , Excipients/chemistry , Male , Hypromellose Derivatives/chemistry , Chemistry, Pharmaceutical/methods , Drug Stability , X-Ray Diffraction/methods
6.
Chin J Integr Med ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39243319

ABSTRACT

OBJECTIVES: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. METHODS: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. RESULTS: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. CONCLUSION: BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.

7.
Best Pract Res Clin Obstet Gynaecol ; 97: 102550, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39243521

ABSTRACT

The World Health Organization includes oral emergency contraception (EC) in the list of essential medicines. Ulipristal acetate (UPA) and levonorgestrel (LNG) are the recommended oral methods. UPA has superior efficacy and a comparable side effect profile compared with LNG. Both work by inhibiting or delaying ovulation, so that sperm present in the reproductive tract will have lost their fertilising ability by the time the oocyte is eventually released. Neither LNG nor UPA at the EC doses have significant effects on the endometrium and are unable to prevent implantation. Mifepristone can also be used for EC but its availability is limited to few countries. LNG is less effective in women with a body mass index over 26 kg/m2 or weight over 70 kg. Hormonal contraception can be quickstarted immediately following LNG, or five days following UPA. LNG-releasing intrauterine devices and cyclo-oxygenase inhibitors are promising options for EC to be further studied.

8.
Sci Rep ; 14(1): 21024, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39251625

ABSTRACT

A new conducting polymer of the cellulose acetate poly acrylonitrile (CAPA)-SiC composite was produced using an in situ oxidative polymerization technique in an aqueous medium. SiC was synthesized from Cinachyrella sp. as a source of carbon and silicon at 1200 °C under an argon atmosphere via a catalytic reduction process. The structure and morphology of the CAPA-SiC composite were characterized using surface area studies (BET), X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), and surface morphology (SEM & TEM). To protect copper, the produced CAPA-SiC composite was mixed with commercial epoxy paint using a casting technique, and the copper surface was coated with the three components of the CAPA-SiC/epoxy paint mixture. The corrosion inhibition improvement of the CAPA-SiC/paint coating was assessed using electrochemical impedance spectroscopy followed by Tafel polarization measurements in a 3.5 wt% NaCl solution. The corrosion protection ability of the CAPA-SiC/epoxy coating was found to be outstanding at 97.4% when compared to that of a CAPA/paint coating. SEM and XRD were used to illustrate the coating on the copper surface.

9.
Int J Pharm X ; 8: 100271, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39252691

ABSTRACT

This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from silicone-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.

10.
Dent Traumatol ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258436

ABSTRACT

BACKGROUND/OBJECTIVES: The use of different models for the fabrication of custom-fit mouthguards (MTGs) can affect their final thickness, adaptation, and shock-absorption properties. This study aimed to evaluate the adaptation, thickness, and shock absorption of ethylene-vinyl acetate (EVA) thermoplastic MTGs produced using conventional plaster or three-dimensional (3D) printed models. MATERIALS AND METHODS: A typical model with simulated soft gum tissue was used as the reference model to produce MTGs with the following two different protocols: plast-MTG using a conventional impression and plaster model (n = 10) and 3DPr-MTG using a digital scanning and 3D printed model (n = 10). A custom-fit MTG was fabricated using EVA sheets (Bioart) plasticized over different models. The MTG thickness (mm), internal adaptation (mm) to the typodontic model, and voids in the area (mm2) between the two EVA layers were measured using cone-beam computed tomography images and Mimics software (Materialize). The shock absorption of the MTG was measured using a strain-gauge test with a pendulum impact at 30° with a steel ball over the typodont model with and without MTGs. Data were analyzed using one-way analysis of variance with repeated measurements, followed by Tukey's post hoc tests. RESULTS: The 3DPr-MTG showed better adaptation than that of the Plast-MTG at the incisal/occlusal and lingual tooth surfaces (p < 0.001). The 3DPr-MTG showed a thickness similar to that of the Plast-MTG, irrespective of the measured location. MTGs produced using both model types significantly reduced the strain values during horizontal impact (3DPr-MTG 86.2% and Plast-MTG 87.0%) compared with the control group without MTG (p < 0.001). CONCLUSION: The MTGs showed the required standards regarding thickness, adaptation, and biomechanical performance, suggesting that the number and volume of voids had no significant impact on their functionality. Three-dimensional printed models are a viable alternative for MTG production, providing better adaptation than the Plast-MTG at the incisal/occlusal and lingual tooth surfaces and similar performance as the MTG produced with the conventional protocol.

11.
Cureus ; 16(8): e66454, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39246969

ABSTRACT

Introduction Through its National Family Planning Programme, India has been relentlessly working to decrease society's unmet contraception needs. The postpartum period is of paramount importance for addressing these contraceptive needs owing to alterations in fertility and coital behavior associated with childbirth. Depot medroxyprogesterone acetate (DMPA), a long-acting reversible contraceptive, is one of the safe options available in the early postpartum period. In this study, we aimed to evaluate its efficacy and acceptability among postpartum women delivering in Guru Gobind Singh Medical College and Hospital. Methodology We recruited 206 early postpartum women for the study. After thorough counseling and ensuring establishment of lactation, we administered DMPA 150mg by injection intramuscularly and repeated it at intervals of three months in willing patients. We then evaluated them for their symptoms, side effects, and lactation status using a predesigned proforma either during their follow-up visits or telephonically. Results We found DMPA to be 100% efficacious as an early postpartum contraceptive measure. The main reasons for acceptance were its ease of use, long-term effects of a single dose, and noninterference with lactation. However, the continuation rate for the second dose was only 18% in our study, highlighting the need for better counseling and improving awareness among our patients. Ninety-nine percent of our patients were satisfied with their lactation. Conclusion We found injectable DMPA used as a contraceptive in the immediate postpartum period to be a safe and effective alternate method with no deleterious effect on lactation and an acceptable side effect profile. However, more awareness programs are necessary to encourage women, especially those in low-resource areas, to continue using DMPA.

12.
Bioresour Technol ; 413: 131437, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39244107

ABSTRACT

The carbon and energy efficiency of a biomanufacturing process is of crucial importance in determining its economic viability. Formate dehydrogenase has been demonstrated to be beneficial in regenerating NADH from formate produced during sugar metabolism, thereby creating energy-efficient systems. Nevertheless, introducing enzyme(s) for butyryl butyrate (BB) biosynthesis based on this system, only 1.64 g/L BB with 14.3 % carbon yield was obtained due to an imbalance in NADH-NAD+ turnover. To address the issue of NADH accumulation, a joint redox-balanced pathway for BB biosynthesis was developed in this study by coupling acetate and glucose metabolism. Following overexpression of acetyl-CoA synthetase in the BB-producing strain, acetate and glucose were co-utilized stoichiometrically and intracellular redox homeostasis was achieved. The engineered strain produced 29.02 g/L BB with carbon yield of 43.3 %, representing the highest yield ever reported for fermentative production of BB. It indicated the potential for developing a carbon- and energy-effective route for biomanufacturing.

13.
Article in English | MEDLINE | ID: mdl-39243813

ABSTRACT

The administration of intravenous fluids is the most common intervention in hospitalised patients in the perioperative setting and critical care units. The aim of this narrative review is to provide an overview of balanced solutions for fluid therapy in the perioperative period in adult patients, and to review new trends and solutions in fluid therapy. The evidence was grouped into 3 areas: intraoperative fluid administration, fluid administration in critically ill patients, and the importance / benefit of balanced crystalloid solutions. Although a number of high-quality studies have been published in recent years, the scientific evidence regarding the type of fluid, the dose, and rate of administration is still limited. The choice of fluid therapy during the perioperative period must be tailored to patient-specific factors, the nature of the surgery, expected fluid loss, and other relevant factors. Finally, more robust clinical evidence and physician training is of the utmost importance.

14.
Clin Genitourin Cancer ; 22(6): 102200, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39244832

ABSTRACT

INTRODUCTION: The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). MATERIALS AND METHODS: We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). RESULTS: Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. CONCLUSION: Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

15.
Microb Cell Fact ; 23(1): 238, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39223542

ABSTRACT

BACKGROUND: Benzyl acetate is an aromatic ester with a jasmine scent. It was discovered in plants and has broad applications in food, cosmetic, and pharmaceutical industries. Its current production predominantly relies on chemical synthesis. In this study, Escherichia coli was engineered to produce benzyl acetate. RESULTS: Two biosynthetic routes based on the CoA-dependent ß-oxidation pathway were constructed in E. coli for benzyl acetate production. In route I, benzoic acid pathway was extended to produce benzyl alcohol by combining carboxylic acid reductase and endogenous dehydrogenases and/or aldo-keto reductases in E. coli. Benzyl alcohol was then condensed with acetyl-CoA by the alcohol acetyltransferase ATF1 from yeast to form benzyl acetate. In route II, a plant CoA-dependent ß-oxidation pathway via benzoyl-CoA was assessed for benzyl alcohol and benzyl acetate production in E. coli. The overexpression of the phosphotransacetylase from Clostridium kluyveri (CkPta) further improved benzyl acetate production in E. coli. Two-phase extractive fermentation in situ was adopted and optimized for benzyl acetate production in a shake flask. The most optimal strain produced 3.0 ± 0.2 g/L benzyl acetate in 48 h by shake-flask fermentation. CONCLUSIONS: We were able to establish the whole pathway for benzyl acetate based on the CoA-dependent ß-oxidation in single strain for the first time. The highest titer for benzyl acetate produced from glucose by E. coli is reported. Moreover, cinnamyl acetate production as an unwanted by-product was very low. Results provided novel information regarding the engineering benzyl acetate production in microorganisms.


Subject(s)
Escherichia coli , Glucose , Metabolic Engineering , Metabolic Engineering/methods , Escherichia coli/metabolism , Escherichia coli/genetics , Glucose/metabolism , Fermentation , Acetates/metabolism , Oxidation-Reduction , Acetyl Coenzyme A/metabolism , Oxidoreductases/metabolism , Oxidoreductases/genetics , Benzyl Compounds/metabolism
16.
Food Chem X ; 23: 101743, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39257489

ABSTRACT

Black tea is highly favored by consumers worldwide, with enzymatic reactions being recognized as a pivotal factor influencing tea quality. The role of microorganisms in shaping the composition of black tea has emerged as a focus of research due to their involvement in enzyme catalysis and metabolic processes. In this study, full-length amplicon sequencing combined with qPCR more accurately reflected microbial profile, and Pantoea, Pseudomonas, Paucibacter, and Cladosporium were identified as the main microbial genera. Moreover, by comprehensively analyzing color, aroma, and taste components over time in black tea samples, correlations were established between the dominant genus and various quality factors. Notably, peroxidase activity levels, total soluble sugar content, and tea pigments concentration exhibited significant associations with the dominant genus. Consequently, this microbiological perspective facilitated the exploration of driving factors for improving black tea quality while establishing a theoretical foundation for quality control in industrial production.

17.
Front Oncol ; 14: 1412021, 2024.
Article in English | MEDLINE | ID: mdl-39224801

ABSTRACT

We report the case of a 54-year-old healthy Han Chinese male presenting with fever, pallor, erythematous subcutaneous nodules on the limbs, and significant anemia as indicated by routine blood tests, with no response to antimicrobial therapy. Initial skin biopsy was inconclusive. The erythematous subcutaneous nodules on the limbs rapidly progressed to widespread subcutaneous nodules across the body, with worsening anemia. Bone marrow biopsy revealed multifocal fibroblastic proliferation with focal fibrosis, classified as MF-2, and positive for the JAK2V617F mutation alongside SRSF2 positivity. Whole-body PET-CT scans did not reveal any lymph nodes or suspect lesions with high SUV uptake. A subsequent skin biopsy identified the condition as nodular panniculitis (NP), leading to a final diagnosis of primary myelofibrosis(PMF)with NP. The patient initially received treatment with oral ruxolitinib and prednisone acetate, resulting in normalization of body temperature, resolution of erythematous nodules, and normalization of blood parameters.

18.
Int Immunopharmacol ; 142(Pt A): 112968, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39226827

ABSTRACT

INTRODUCTION: Lead acetate (PbAc), a hazardous heavy metal, poses significant threats to human health and the environment because of widespread industrial exposure. PbAc exposure leads to liver injury primarily through oxidative stress and the disruption of key regulatory pathways. Understanding these mechanisms and exploring protective agents are vital for mitigating PbAc-induced hepatotoxicity. Therefore, we aimed to investigate the molecular pathways implicated in PbAc-induced liver damage, focusing on Sirt-1, Nrf2 (HO-1, NQO1, and SOD), Akt-1/GSK3ß, m-TOR, and P53. Additionally, we aimed to assess the hepatoprotective effects of arbutin, which is administered orally and intraperitoneally, to determine the most effective delivery method. METHODOLOGY: In silico analyses were conducted to identify relevant protein networks associated with Sirt-1 and AKT-1/GSK-3B pathways. The pharmacodynamic properties of arbutin were examined, followed by molecular docking studies to elucidate its interactions with the selected protein network. In vivo preclinical studies were carried out on adult male rats randomly assigned to 6 different treatment groups, including PbAc exposure and PbAc exposure treated with arbutin either orally or intraperitoneally. RESULTS: PbAc exposure led to hepatic oxidative stress, as evidenced by elevated MDA levels and SIRT-1 inhibition, disrupting antioxidant pathways and activating antiautophagic and proapoptotic pathways, ultimately resulting in hepatocyte necrosis. Both oral and intraperitoneal arbutin administration effectively modifed these effects, with intraperitoneal delivery showing superior efficacy in mitigating PbAc-induced histological, immunological, and biochemical alterations. CONCLUSION: This study provides insights into the molecular mechanisms underlying PbAc-induced liver injury and highlights the hepatoprotective potential of arbutin. These findings suggest that arbutin, particularly when administered intraperitoneally, holds promise as a therapeutic agent for combating PbAc-induced hepatotoxicity.

19.
Carbohydr Polym ; 345: 122560, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227099

ABSTRACT

This work studied the phase transition and gel properties of cassava starch in aqueous choline acetate ([Ch][OAc]) solution at different [Ch][OAc]:water weight ratios. The paste viscosity and gel strength followed a similar pattern to the starch phase transition temperature, increasing at a 2:3 [Ch][OAc]:water ratio and then decreasing at 3:2 and 4:1 ratios. However, the mobility of free water in the starch gel decreased as the [Ch][OAc]:water ratio increased. At the same [Ch][OAc]:water ratios, acetylated cassava starch (ACS) underwent phase transition more easily than native cassava starch (NCS), leading to greater granule destruction. Nevertheless, ACS gels displayed more viscous-dominated rheological behavior, lower paste viscosity, viscoelasticity, and weaker water-holding capacity (WHC) than NCS gels. In contrast, cross-linked cassava starch (CCS) gels had higher paste viscosity, gel viscoelasticity, and WHC. However, at a 4:1 [Ch][OAc]:water ratio, the viscoelasticity of CCS gel was lower than NCS gel, and the differences in WHC were minimal, likely due to the incomplete phase transition of especially CCS under this condition. Our findings show that starch chemical modification significantly affects phase transition behavior and gel properties in [Ch][OAc]:water mixtures, with outcomes influenced by the viscosity of the aqueous [Ch][OAc] solution and the interaction between [Ch][OAc] and water.

20.
Cureus ; 16(8): e66005, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39221354

ABSTRACT

Study objective The purpose of this study is to investigate the analgesic efficacy of ultrasound-guided fascial plane blocks (FPBs) versus local infiltration in patients undergoing laparoscopic non-donor nephrectomy. This study specifically compares the efficacy of FPBs with liposomal bupivacaine (LB) versus FPBs with dexamethasone sodium phosphate (DXP) and methylprednisolone acetate (MPA) versus surgical site local anesthetic infiltration without FPBs.  Design This is a retrospective cohort study conducted over a five-year period (January 2018-December 2022). Setting The study was conducted in a tertiary care, academic, multi-hospital healthcare system.  Participants Patients who underwent elective radical or partial laparoscopic non-donor nephrectomy were included in the study. Intervention Patients either received preoperative FPBs without intraoperative surgical site local anesthetic infiltration or received surgical site local anesthetic infiltration without FPBs (n = 141) at participating hospitals. Measurements The primary endpoint of this study was postoperative opioid use, measured as oral milligram morphine equivalents (MME). Secondary endpoints included postoperative pain scores, length of hospital stays, and significant adverse events within 30 days. The impact of medications utilized in FPBs was determined by univariate and multivariable analyses with covariates balancing propensity score weighting. Main results Patients undergoing non-donor laparoscopic radical or partial nephrectomy who received FPBs with bupivacaine or ropivacaine plus glucocorticoids DXP and MPA were more likely to be opioid-free 24-48 hours postoperatively compared to those who received FPBs with LB or surgical site local anesthetic infiltration without FPBs (40.5% vs. 30% vs. 13.9%, respectively; p = 0.017). Patients who received FPBs with glucocorticoids also reported the lowest pain scores at rest and with activity 0-12 hours postoperatively as compared to patients who received LB or local infiltration (p = 0.006 and p = 0.014, respectively). Additionally, patients who received FPBs with glucocorticoids received over 30% fewer opioids during the first 48 hours postoperatively compared to patients who received surgical site local anesthetic infiltration alone (30 MME vs. 44 MME, respectively). However, there was no significant difference in total opioid use during the first 48 hours postoperatively between patients who received FPBs with bupivacaine plus glucocorticoids and those who received FPBs with bupivacaine plus LB (mean ratio: 0.91, (95% CI: 0.05 ~ 15.97); p = 0.948). There was also no difference in the length of hospital stays or rate of adverse events between the groups. Conclusion Perioperative FPBs for non-donor laparoscopic nephrectomy using glucocorticoids as an adjuvant to long-acting local anesthetics may decrease postoperative opioid use and reduce pain scores as compared to FPBs with LB or surgical site local anesthetic infiltration. Bupivacaine or ropivacaine combined with DXP and MPA is a safe and effective alternative to LB for FPBs in laparoscopic nephrectomy.

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